Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity

 Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the −174G/C promoter polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the T → C polymorphism in intron 5 of the transforming growth factor β₁ (TGF-β₁) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms of these five markers with other populations using the χ² test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were identified. For the −174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A ₁ at the Sp1, Asn363Ser, and T → C marker sites that have been found to be polymorphic in other populations were not found in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms (P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers in osteoporosis genetic research in other populations. Received: April 22, 2002 / Accepted: July 2, 2002 Acknowledgments. The study was partially supported by the Hunan Province Special Professor Start-up Fund (25000612), Chinese National Science Foundation (CNSF) Outstanding Young Scientist Award (30025025), CNSF Grant (30170504), a grant from Huo Ying-Dong Education Foundation, and a Seed Fund from the Ministry of Education of P.R. China (25000106). Some investigators (R.R.R., V.D., H.W.D.) were partially supported by grants from the Health Future Foundation of USA, grants of National Health Institute (K01 AR02170-01, R01 GM60402-01A1), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program, and U.S. Department of Energy grant (DE-FG03-00ER63000/A00). We thank all the study subjects for volunteering to participate in the study. Offprint requests to: H.-W. Deng